Efficacy and Safety of Liraglutide in Combination With Metformin Compared to Metformin Alone, in Children and Adolescents With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— Ellipse™  

Official title:

Efficacy and Safety of Liraglutide in Combination With Metformin Versus Metformin Monotherapy on Glycaemic Control in Children and Adolescents With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01541215
• Other study ID #: NN2211-3659
• Secondary ID: 2011-002605-29P/
• Status: Completed
• Phase: Phase 3
• Start date: November 13, 2012
• Est. completion date: May 20, 2020

Study information

• Verified date: July 2021
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted globally. The aim of this trial is to assess the efficacy and safety of liraglutide in the paediatric population in order to potentially address the unmet need for treatment of children and adolescents with type 2 diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: May 20, 2020
• Est. primary completion date: November 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

Inclusion Criteria: - Children and adolescents between the ages of 10-16 years. Subjects cannot turn 17 years and 11 months before the end of treatment (52 weeks) - Diagnosis of type 2 diabetes mellitus and treated for at least 30 days with: diet and exercise alone, diet and exercise in combination with metformin monotherapy, diet and exercise in combination with metformin and a stable (Stable is defined as basal insulin adjustments up to 15%) dose of basal insulin, diet and exercise in combination with a stable (Stable is defined as basal insulin adjustments up to 15%) dose of basal insulin - HbA1c: 7.0-11% (inclusive) if diet and exercise treated or 6.5-11% (inclusive) if treated with metformin as monotherapy, basal insulin as monotherapy or metformin and basal insulin in combination

• Body mass index (BMI) above 85% percentile of the general age and gender matched population Exclusion Criteria: - Type 1 diabetes - Maturity onset diabetes of the young (MODY) - Use of any antidiabetic agent other than metformin and/or basal insulin within 90 days prior to screening - Recurrent severe hypoglycaemia or hypoglycaemic unawareness as judged by the investigator - History of chronic pancreatitis or idiopathic acute pancreatitis - Any clinically significant disorder, except for conditions associated with type 2 diabetes history which in the investigator's opinion could interfere with results of the trial - Uncontrolled hypertension, treated or untreated above 99th percentile for age and gender in children - Known or suspected abuse of alcohol or drugs/narcotics

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• liraglutide
Administered subcutaneously (s.c., under the skin) once daily.1.8 mg or maximum tolerated dose (MTD: 0.6 mg, 1.2 mg, 1.8 mg) for 26 weeks. Subjects will continue treatment in a 26 week open-labelled extension. Rescue treatment will be allowed if rescue criteria are met.
• placebo
Administered subcutaneously (s.c., under the skin) once daily for 26 weeks. Subjects will discontinue placebo treatment in the open-labelled extension. Rescue treatment will be allowed if rescue criteria are met.
• metformin
Tablets administered for 26 weeks. Maximum tolerated dose (MTD) between 1000-2000 mg at the discretion of the investigator. Subjects will continue treatment in a 26 week open-labelled extension.

Locations

Country	Name	City	State
Australia	Novo Nordisk Investigational Site	Ipswich	Queensland
Austria	Novo Nordisk Investigational Site	Graz
Austria	Novo Nordisk Investigational Site	Innsbruck
Austria	Novo Nordisk Investigational Site	Salzburg
Austria	Novo Nordisk Investigational Site	Wels
Belgium	Novo Nordisk Investigational Site	Brussel
Belgium	Novo Nordisk Investigational Site	Bruxelles
Belgium	Novo Nordisk Investigational Site	Leuven
Brazil	Novo Nordisk Investigational Site	Porto Alegre	Rio Grande Do Sul
Canada	Novo Nordisk Investigational Site	Brampton	Ontario
Canada	Novo Nordisk Investigational Site	Edmonton	Alberta
Canada	Novo Nordisk Investigational Site	Westmount	Quebec
Canada	Novo Nordisk Investigational Site	Winnipeg	Manitoba
Croatia	Novo Nordisk Investigational Site	Rijeka
Croatia	Novo Nordisk Investigational Site	Zagreb
Denmark	Novo Nordisk Investigational Site	Herlev
Denmark	Novo Nordisk Investigational Site	Næstved
Egypt	Novo Nordisk Investigational Site	Alexandria
Egypt	Novo Nordisk Investigational Site	Cairo
Egypt	Novo Nordisk Investigational Site	Cairo
Egypt	Novo Nordisk Investigational Site	Mansoura
France	Novo Nordisk Investigational Site	Marseille
France	Novo Nordisk Investigational Site	MONTPELLIER cedex 05
Germany	Novo Nordisk Investigational Site	Ludwigshafen
Germany	Novo Nordisk Investigational Site	Mayen
Greece	Novo Nordisk Investigational Site	Athens
Greece	Novo Nordisk Investigational Site	Athens
Greece	Novo Nordisk Investigational Site	Goudi/ Athens
Greece	Novo Nordisk Investigational Site	Thessaloniki
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Miskolc
Hungary	Novo Nordisk Investigational Site	Szombathely
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Chandigarh	Punjab
India	Novo Nordisk Investigational Site	Chennai	Tamil Nadu
India	Novo Nordisk Investigational Site	Guntur	Andhra Pradesh
India	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh
India	Novo Nordisk Investigational Site	Hyderbad	Telengana
India	Novo Nordisk Investigational Site	Jaipur	Rajasthan
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Kolkata
India	Novo Nordisk Investigational Site	Ludhiana	Punjab
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	New Dehli	New Delhi
India	Novo Nordisk Investigational Site	Pune	Maharashtra
Israel	Novo Nordisk Investigational Site	Beer Sheva
Israel	Novo Nordisk Investigational Site	Haifa
Israel	Novo Nordisk Investigational Site	Jerusalem
Israel	Novo Nordisk Investigational Site	Petah Tikva
Israel	Novo Nordisk Investigational Site	Tel Hashomer
Italy	Novo Nordisk Investigational Site	Roma
Lebanon	Novo Nordisk Investigational Site	Hazmieh
Lebanon	Novo Nordisk Investigational Site	Lebanon - Beirut
Malaysia	Novo Nordisk Investigational Site	Kuala Lumpur
Mexico	Novo Nordisk Investigational Site	Puebla
Mexico	Novo Nordisk Investigational Site	Tampico	Tamaulipas
Morocco	Novo Nordisk Investigational Site	Fès
Morocco	Novo Nordisk Investigational Site	Rabat
Netherlands	Novo Nordisk Investigational Site	Den Bosch
New Zealand	Novo Nordisk Investigational Site	Grafton
North Macedonia	Novo Nordisk Investigational Site	Skopje
Norway	Novo Nordisk Investigational Site	Bergen
Poland	Novo Nordisk Investigational Site	Katowice
Poland	Novo Nordisk Investigational Site	Warszawa
Poland	Novo Nordisk Investigational Site	Wroclaw
Portugal	Novo Nordisk Investigational Site	Braga
Portugal	Novo Nordisk Investigational Site	Lisboa
Portugal	Novo Nordisk Investigational Site	Lisboa
Puerto Rico	Novo Nordisk Investigational Site	Ponce
Romania	Novo Nordisk Investigational Site	Bucharest
Romania	Novo Nordisk Investigational Site	Bucharest
Romania	Novo Nordisk Investigational Site	Constanta
Romania	Novo Nordisk Investigational Site	Timisoara	Timis
Russian Federation	Novo Nordisk Investigational Site	Chelyabinsk
Russian Federation	Novo Nordisk Investigational Site	Izhevsk
Russian Federation	Novo Nordisk Investigational Site	Krasnoyarsk
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Novosibirsk
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saratov
Russian Federation	Novo Nordisk Investigational Site	Tomsk
Serbia	Novo Nordisk Investigational Site	Belgrade
Serbia	Novo Nordisk Investigational Site	Belgrade
Serbia	Novo Nordisk Investigational Site	Nis
Serbia	Novo Nordisk Investigational Site	Novi Sad
Spain	Novo Nordisk Investigational Site	Leganés
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Vigo
Spain	Novo Nordisk Investigational Site	Vitoria
Sweden	Novo Nordisk Investigational Site	Göteborg
Sweden	Novo Nordisk Investigational Site	Huddinge
Sweden	Novo Nordisk Investigational Site	Uppsala
Taiwan	Novo Nordisk Investigational Site	Tainan city
Taiwan	Novo Nordisk Investigational Site	Taoyuan
Thailand	Novo Nordisk Investigational Site	Bangkok
Thailand	Novo Nordisk Investigational Site	Chiang Mai
Turkey	Novo Nordisk Investigational Site	Ankara
Turkey	Novo Nordisk Investigational Site	Ankara
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Kocaeli
United Kingdom	Novo Nordisk Investigational Site	Birmingham
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	Manchester
United Kingdom	Novo Nordisk Investigational Site	Norwich
United Kingdom	Novo Nordisk Investigational Site	Southampton
United States	Novo Nordisk Investigational Site	Amarillo	Texas
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Birmingham	Alabama
United States	Novo Nordisk Investigational Site	Bloomington	Indiana
United States	Novo Nordisk Investigational Site	Buffalo	New York
United States	Novo Nordisk Investigational Site	Charleston	West Virginia
United States	Novo Nordisk Investigational Site	Charlottesville	Virginia
United States	Novo Nordisk Investigational Site	Chattanooga	Tennessee
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Columbia	Missouri
United States	Novo Nordisk Investigational Site	Columbus	Georgia
United States	Novo Nordisk Investigational Site	Corona	California
United States	Novo Nordisk Investigational Site	Costa Mesa	California
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Detroit	Michigan
United States	Novo Nordisk Investigational Site	Edinburg	Texas
United States	Novo Nordisk Investigational Site	Fort Worth	Texas
United States	Novo Nordisk Investigational Site	Grand Rapids	Michigan
United States	Novo Nordisk Investigational Site	Greenville	South Carolina
United States	Novo Nordisk Investigational Site	Hackensack	New Jersey
United States	Novo Nordisk Investigational Site	Hershey	Pennsylvania
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Iowa City	Iowa
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Kansas City	Missouri
United States	Novo Nordisk Investigational Site	Kerrville	Texas
United States	Novo Nordisk Investigational Site	Las Vegas	Nevada
United States	Novo Nordisk Investigational Site	Lexington	Kentucky
United States	Novo Nordisk Investigational Site	Lexington	Kentucky
United States	Novo Nordisk Investigational Site	Long Beach	California
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Melbourne	Florida
United States	Novo Nordisk Investigational Site	Memphis	Tennessee
United States	Novo Nordisk Investigational Site	Memphis	Tennessee
United States	Novo Nordisk Investigational Site	Memphis	Tennessee
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Moreno Valley	California
United States	Novo Nordisk Investigational Site	Nashville	Tennessee
United States	Novo Nordisk Investigational Site	New Haven	Connecticut
United States	Novo Nordisk Investigational Site	New York	New York
United States	Novo Nordisk Investigational Site	New York	New York
United States	Novo Nordisk Investigational Site	New York	New York
United States	Novo Nordisk Investigational Site	Norfolk	Virginia
United States	Novo Nordisk Investigational Site	Palo Alto	California
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania
United States	Novo Nordisk Investigational Site	Rapid City	South Dakota
United States	Novo Nordisk Investigational Site	Saint Louis	Missouri
United States	Novo Nordisk Investigational Site	Saint Paul	Minnesota
United States	Novo Nordisk Investigational Site	Saint Petersburg	Florida
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	San Diego	California
United States	Novo Nordisk Investigational Site	Silver Spring	Maryland
United States	Novo Nordisk Investigational Site	Sleepy Hollow	New York
United States	Novo Nordisk Investigational Site	Tallahassee	Florida
United States	Novo Nordisk Investigational Site	Tampa	Florida
United States	Novo Nordisk Investigational Site	Toledo	Ohio
United States	Novo Nordisk Investigational Site	Topeka	Kansas
United States	Novo Nordisk Investigational Site	Tucson	Arizona
United States	Novo Nordisk Investigational Site	Ventura	California
United States	Novo Nordisk Investigational Site	Washington	District of Columbia
United States	Novo Nordisk Investigational Site	West Orange	New Jersey
United States	Novo Nordisk Investigational Site	Wilmington	Delaware
United States	Novo Nordisk Investigational Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Croatia,  Denmark,  Egypt,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Lebanon,  Malaysia,  Mexico,  Morocco,  Netherlands,  New Zealand,  North Macedonia,  Norway,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Serbia,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

References & Publications (1)

Tamborlane WV, Barrientos-Pérez M, Fainberg U, Frimer-Larsen H, Hafez M, Hale PM, Jalaludin MY, Kovarenko M, Libman I, Lynch JL, Rao P, Shehadeh N, Turan S, Weghuber D, Barrett T; Ellipse Trial Investigators. Liraglutide in Children and Adolescents with Type 2 Diabetes. N Engl J Med. 2019 Aug 15;381(7):637-646. doi: 10.1056/NEJMoa1903822. Epub 2019 Apr 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c (Glycosylated Haemoglobin)	Change in HbA1c from baseline to week 26. All available data were used for the primary analysis, including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG)	Change in FPG from baseline to week 26. All available data were used for the analysis, including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Number of Subjects Having HbA1c Below 7.0%	Percentage of subjects having HbA1c <7.0%. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 26
Secondary	Change From Baseline in Body Mass Index (BMI) Standard Deviation Score (SDS)	Change in BMI SDS from baseline to week 26. BMI SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' BMI provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the world health organisation (WHO) Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Number of Subjects Having HbA1c Below 7.0%	Number of subjects achieving HbA1c <7.0% after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 52
Secondary	Number of Subjects Having HbA1c Maximum 6.5%	Number of subjects achieving HbA1c <=6.5% after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 26
Secondary	Number of Subjects Having HbA1c Maximum 6.5%	Number of subjects achieving HbA1c <=6.5% after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 52
Secondary	Number of Subjects Having HbA1c Below 7.0% Without Severe or Minor Hypoglycaemic Episodes	Number of subjects achieving HbA1c <7.0% without severe or minor hypoglycaemic episodes after 26 weeks.; Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.; Minor hypoglycaemia was defined as meeting either of the below criteria: an episode with symptoms consistent with hypoglycaemia with confirmation by blood glucose <2.8 mmol/L (50 mg/dL) or plasma glucose <3.1 mmol/L (56 mg/dL), and which was handled by the subject him/herself; any asymptomatic blood glucose value <2.8 mmol/L (50 mg/dL) or plasma glucose value <3.1 mmol/L (56 mg/dL) All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 26
Secondary	Number of Subjects Having HbA1c Below 7.0% Without Severe or Minor Hypoglycaemic Episodes	Number of subjects achieving HbA1c <7.0% without severe or minor hypoglycaemic episodes after 52 weeks.; Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.; Minor hypoglycaemia was defined as meeting either of the below criteria: an episode with symptoms consistent with hypoglycaemia with confirmation by blood glucose <2.8 mmol/L (50 mg/dL) or plasma glucose <3.1 mmol/L (56 mg/dL), and which was handled by the subject him/herself; any asymptomatic blood glucose value <2.8 mmol/L (50 mg/dL) or plasma glucose value <3.1 mmol/L (56 mg/dL) All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 52
Secondary	Number of Subjects Having HbA1c Below 7.5%	Number of subjects achieving HbA1c <7.5% after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 26
Secondary	Number of Subjects Having HbA1c Below 7.5%	Number of subjects achieving HbA1c <7.5% after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 52
Secondary	Change in HbA1c	Change in HbA1c from baseline to week 52. All available data were used for the analysis, including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Change in FPG	Change in FPG from baseline to week 52. All available data were used for the analysis, including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Change in Mean 7-point Self-measured Plasma Glucose	Change in mean 7-point self-measured plasma glucose after 26 weeks. Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime. Mean 7-point SMPG was defined as the area under the profile (calculated using the trapezoidal method) divided by time. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Change From Baseline in 7-point Self-measured Plasma Glucose	Change in mean 7-point self-measured plasma glucose after 52 weeks. Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime. Mean 7-point SMPG was defined as the area under the profile (calculated using the trapezoidal method) divided by time. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Change in Post-prandial Increments (From Before Meal to 90 Min After Breakfast, Lunch, and Dinner)	Change in post-prandial increments (from before meal to 90 min after breakfast, lunch, and dinner) after 26 weeks. Post-prandial increment for each meal (breakfast, lunch, and dinner) was derived from the 7-point SMPG profile as the difference between post-prandial plasma glucose values and the plasma glucose values before the meal. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Change in Post-prandial Increments (From Before Meal to 90 Min After Breakfast, Lunch, and Dinner)	Change in post-prandial increments (from before meal to 90 min after breakfast, lunch, and dinner) after 52 weeks. Post-prandial increment for each meal (breakfast, lunch, and dinner) was derived from the 7-point SMPG profile as the difference between post-prandial plasma glucose values and the plasma glucose values before the meal. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Change in Mean Post-prandial Increment Across All Three Meals (Breakfast, Lunch, and Dinner)	Change in mean post-prandial increment across all three meals (breakfast, lunch, and dinner) after 26 weeks. Post-prandial increment for each meal (breakfast, lunch, and dinner) was derived from the 7-point SMPG profile as the difference between post-prandial plasma glucose values and the plasma glucose values before the meal. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Change in Mean Post-prandial Increment Across All Three Meals (Breakfast, Lunch, and Dinner)	Change in mean post-prandial increment across all three meals (breakfast, lunch, and dinner) after 52 weeks. Post-prandial increment for each meal (breakfast, lunch, and dinner) was derived from the 7-point SMPG profile as the difference between post-prandial plasma glucose values and the plasma glucose values before the meal. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Change From Baseline in Body Weight	Change from baseline in body weight after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Change From Baseline in Body Weight	Change from baseline in body weight after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Change From Baseline in BMI Standard Deviation Score (SDS)	Change in BMI SDS from baseline to week 52. BMI SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' BMI provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Change in Blood Pressure (Systolic and Diastolic Blood Pressure)	Change in blood pressure (systolic and diastolic blood pressure) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Change in Blood Pressure (Systolic and Diastolic Blood Pressure)	Change in blood pressure (systolic and diastolic blood pressure) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: Fasting Insulin	Ratio to baseline (fasting insulin) at week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: Fasting Insulin	Ratio to baseline (fasting insulin) at week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: Fasting Pro-insulin	Ratio to baseline (fasting pro-insulin) at week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: Fasting Pro-insulin	Ratio to baseline (fasting pro-insulin) at week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: Pro-insulin/Insulin Ratio	Ratio to baseline (Pro-insulin/insulin ratio) after week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: Pro-insulin/Insulin Ratio	Ratio to baseline (Pro-insulin/insulin ratio) after week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: Fasting Glucagon	Ratio to baseline (fasting glucagon) at week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: Fasting Glucagon	Ratio to baseline (fasting glucagon) at week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: Fasting C-peptide	Ratio to baseline (fasting C-peptide) at week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: Fasting C-peptide	Ratio to baseline (fasting C-peptide) at week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: Homeostasis Model Assessment of Beta-cell Function (HOMA-B)	Ratio to baseline (HOMA-B) after 26 weeks. HOMA-B is an index of beta-cell function and was calculated from fasting insulin. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: HOMA-B	Ratio to baseline (HOMA-B) after 52 weeks. HOMA-B is an index of beta-cell function and was calculated from fasting insulin. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: Homeostasis Model Assessment as an Index of Insulin Resistance (HOMA-IR)	Ratio to baseline (HOMA-IR) after 26 weeks. HOMA-IR is an index of insulin resistance and was calculated from fasting insulin. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: HOMA-IR	Ratio to baseline (HOMA-IR) after 52 weeks. HOMA-IR is an index of insulin resistance and was calculated from fasting insulin. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: Total Cholesterol	Ratio to baseline (total cholesterol) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: Total Cholesterol	Ratio to baseline (total cholesterol) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: Low Density Lipoprotein (LDL) Cholesterol	Ratio to baseline (LDL cholesterol) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: LDL Cholesterol	Ratio to baseline (LDL cholesterol) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: Very Low-density Lipoprotein (VLDL) Cholesterol	Ratio to baseline (VLDL cholesterol) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: VLDL Cholesterol	Ratio to baseline (VLDL cholesterol) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: High-density Lipoprotein (HDL) Cholesterol	Ratio to baseline (HDL cholesterol) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: HDL Cholesterol	Ratio to baseline (HDL cholesterol) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: Triglycerides	Ratio to baseline (triglycerides) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: Triglycerides	Ratio to baseline (triglycerides) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Ratio to Baseline: Free Fatty Acids	Ratio to baseline (free fatty acids) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Ratio to Baseline: Free Fatty Acids	Ratio to baseline (free fatty acids) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Change From Baseline in Pulse	Change from baseline in pulse 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Change From Baseline in Pulse	Change from baseline in pulse 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Change From Baseline in Height SDS	Change in height SDS from baseline to week 26. Height SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Change From Baseline in Height SDS	Change in height SDS from baseline to week 52. Height SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Change in Bone Age Assessment (X-ray of Left Hand and Wrist)	Change in bone age from baseline to week 52. If the baseline (week 0) bone age assessment indicated that all epiphyses were fused, then the assessment was not repeated at week 52.	Week 0, week 52
Secondary	Pubertal Assessment/Progression (Tanner Staging)	Pubertal development was assessed in 3 areas (breast, penis and pubic hair development) by the Tanner staging in accordance with stages I-V. The Tanner staging assessment was no longer required to be performed once a subject reached the Tanner stage V, as judged by the investigator. Reported results are number of participants at different Tanner stages at week 0, week 26 and week 52.	Week 0, week 26, week 52
Secondary	Growth (Height Velocity)	Growth (i.e., height velocity) is the change in height per year and is measured in cm/year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by the time (in days) between those measurement time points and multiplied by 365 days.	Week 0, week 26
Secondary	Growth (Height Velocity)	Growth (i.e., height velocity) is the change in height per year and is measured in cm/year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by the time (in days) between those measurement time points and multiplied by 365 days.	Week 0, week 52
Secondary	Height Velocity SDS	Height velocity SDS scores at week 26. Height velocity is change in height per year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 26
Secondary	Height Velocity SDS	Height velocity SDS scores at week 52. Height velocity is change in height per year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.	Week 0, week 52
Secondary	Number of Hypoglycaemic Episodes	Total number of hypoglycaemic episodes according to American Diabetes Association (ADA) classification from baseline (week 0) to week 26.	0-26 weeks
Secondary	Number of Hypoglycaemic Episodes	Total number of hypoglycaemic episodes according to American Diabetes Association (ADA) classification from baseline (week 0) to week 52.	0-52 weeks
Secondary	Number of Adverse Events (Week 0-26)	Total number of adverse events during 26 weeks.	0-26 weeks
Secondary	Number of Adverse Events (Week 0-52)	Total number of adverse events during entire treatment period.	0-52 weeks
Secondary	Number of Serious Adverse Events (Week 0-26)	Total number of serious adverse events during 26 weeks.	0-26 weeks
Secondary	Number of Serious Adverse Events (Week 0-52)	Total number of serious adverse events during entire treatment period.	0-52 weeks
Secondary	Number of Adverse Events (Week 53-104)	This outcome is applicable only for the Liraglutide 1.8 mg treatment arm. Number of adverse events reported during follow-up 1 (week 53 to 104).	Week 53-104
Secondary	Number of Serious Adverse Events (Week 53-104)	This outcome is applicable only for the Liraglutide 1.8 mg treatment arm. Number of serious adverse events reported during follow up 1 (week 53 to 104).	Weeks 53-104
Secondary	Growth (Height Velocity)- Week 104	Growth (i.e., height velocity) is the change in height per year and is measured in cm/year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by the time (in days) between those measurement time points and multiplied by 365 days. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.	Week 0, week 104
Secondary	Height Velocity SDS- Week 104	The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.	Week 0, week 104
Secondary	Change From Week 52 in Height SDS- Week 104	Change in height SDS from week 52 to week 104. Height SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.	Week 52, week 104
Secondary	Change in Pubertal Assessment/Progression (Tanner Staging)- Week 104	Pubertal development was assessed in 3 areas (breast, penis and pubic hair development) by the Tanner staging in accordance with stages I-V, where stage I represents "pre-adoloscent development" and stage V represents "pubertal development equivalent to that of an adult". The Tanner staging assessment was no longer required to be performed once a subject reached the Tanner stage V, as judged by the investigator. Reported results are number of subjects at different Tanner stages at week 52 and week 104. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.	Week 52, week 104
Secondary	Change From Week 52 in Bone Age Assessment (X-ray of Left Hand and Wrist)- Week 104	Change in bone age from week 52 to week 104. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.	Week 52, week 104
Secondary	Number of Adverse Events (Week 53-156)	This outcome measure is applicable only for the Liraglutide 1.8 mg treatment arm. Number of adverse events reported during the follow-up period (weeks 53 to 156).	Week 53-156
Secondary	Number of Serious Adverse Events (Week 53-156)	This outcome measure is applicable only for the Liraglutide 1.8 mg treatment arm. Number of serious adverse events reported during the follow up period (week 53 to 156).	Weeks 53-156
Secondary	Growth (Height Velocity)- Week 156	Growth (i.e., height velocity) is the change in height per year and is measured in cm/year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by the time (in days) between those measurement time points and multiplied by 365 days. This outcome measure is applicable only for the Liraglutide 1.8 mg treatment arm.	Week 0, week 156
Secondary	Height Velocity SDS- Week 156	The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. This outcome measure is applicable only for the Liraglutide 1.8 mg treatment arm.	Week 0, week 156
Secondary	Change From Week 52 in Height SDS- Week 156	Change in height SDS from week 52 to week 156. Height SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication. This outcome measure is applicable only for the Liraglutide 1.8 mg treatment arm.	Week 52, week 156
Secondary	Change in Pubertal Assessment/Progression (Tanner Staging)- Week 156	Pubertal development was assessed in 3 areas (breast, penis and pubic hair development) by the Tanner staging in accordance with stages I-V, where stage I represents "pre-adoloscent development" and stage V represents "pubertal development equivalent to that of an adult". The Tanner staging assessment was no longer required to be performed once a subject reached the Tanner stage V, as judged by the investigator. Reported results are number of subjects at different Tanner stages at week 52 and week 156. This outcome measure is applicable only for the Liraglutide 1.8 mg treatment arm.	Week 52, week 156
Secondary	Change From Week 52 in Bone Age Assessment (X-ray of Left Hand and Wrist)- Week 156	Change in bone age from week 52 to week 156. This outcome measure is applicable only for the Liraglutide 1.8 mg treatment arm.	Week 52, week 156

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